plinabulin (BPI 2358) / BeyondSpring, Jiangsu Hengrui Pharma - LARVOL DELTA

BeyondSpring to Participate at the 12th Annual Immuno-Oncology 360° Conference (GlobeNewswire) - "Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring, will present on Plinabulin as a differentiated immuno-oncology asset designed to enhance PD-1/PD-LD blockade and highlight Plinabulin’s unique mechanism of action and clinical development strategy."

Clinical • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Plinabulin to shorten neutropenia and improve quality of life peri-autologous hematopoietic cell transplant. (ASCO 2023) - P2 | "To decrease the period of myelosuppression and obligate neutropenia after high dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for patients with multiple myeloma, we studied the addition of plinabulin to standard growth factors. To achieve the primary objective of reducing the duration of absolute neutropenia post AHCT, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion (Day 0) with pegfilgrastim on Day +1 in this pilot trial (NCT05130827)... Plinabulin appears well tolerated without additional major toxicities post AHCT and provided a high WBC on Day +2 and decreased rate of neutropenic fever. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to later post AHCT pre engraftment may further shorten the duration of neutropenia using this novel mechanism of action."

HEOR • Bone Marrow Transplantation • Cardiovascular • Chemotherapy-Induced Neutropenia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Immune Modulation • Multiple Myeloma • Neutropenia • Oncology • Solid Tumor • Transplantation • CD34

Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/Metastatic Non-Squamous NSCLC After PD-1/PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4) (clinicaltrials.gov) - P3 | N=442 | Not yet recruiting | Sponsor: BeyondSpring Pharmaceuticals Inc.

New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Plinabulin/Docetaxel vs. Docetaxel in 2L/3L NSCLC after Platinum Regimens (DUBLIN-3): A Phase 3 Randomized Controlled Trial (IASLC-WCLC 2024) - P3 | "Conclusions : In patients with advance EGFR wild-type platinum refractory NSCLC, plinabulin combined with docetaxel was well-tolerated and statistically significantly improved OS/PFS/ORR with reduced severe neutropenia. A durable anti-cancer benefit was observed suggesting that plinabulin/docetaxel as a potential practice-changing treatment for advanced/metastatic NSCLC without driver mutations."

Clinical • P3 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Study of Plinabulin and Pegfilgrastim in People With Multiple Myeloma Undergoing an Autologous Hematopoietic Stem Cell Transplant (AHCT) (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial primary completion date: Nov 2025 ➔ Nov 2026 | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Transplantation • CD34

Plinabulin/docetaxel vs. docetaxel in 2L/3L EGFRwt NSCLC after platinum regimens (DUBLIN-3): Asian subgroup analysis (ESMO Asia 2025) - "In the Asian subgroup analysis, plinabulin/docetaxel significantly improved OS/PFS/ORR with reduced severe neutropenia, especially in NSQ pts. The durable survival benefit is supported by plinabulin's mechanism ofDC maturation and T cell activation. The positive benefit/risk ratio over docetaxel suggests a potential practice-changing treatment."

IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BPI-2358 reprograms immunosuppressive macrophages and impairs leukemic progression in MN1-overexpressing AML In Vivo (ASH 2025) - "This was further supported by asignificant decrease in spleen weight in the BPI-2358-treated group. These findings reinforce thepotential of macrophage reprogramming as a complementary strategy in AML treatment, especially inmolecularly high-risk subtypes such as those associated with MN1 overexpression."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • CD14 • CD163 • CD34 • CD80 • CD86 • IL1B • IL6 • KIT • MN1 • MRC1 • NOS2 • TGFB1 • TNFA

BeyondSpring Announces New Analyses of DUBLIN-3 Phase 3 Study Showing Survival Benefit of Plinabulin + Docetaxel in Post Anti-PD-(L)1 for Non-squamous EGFR WT NSCLC and a Reduction in Brain Metastasis Compared to Docetaxel at NACLC 2025 (GlobeNewswire) - "Median overall survival (OS): DP 15.8 months vs. D 11.7 months (HR=0.55); Median progression-free survival (PFS): DP 5.6 vs. D 3.8 months (HR=0.67); Objective response rate (ORR): 18.2% vs. 8.0%...Post-hoc analysis of DUBLIN-3 intent-to-treat (ITT, N=559) EGFR WT NSCLC population showed additional clinically meaningful benefits for the Plinabulin + docetaxel combination compared to docetaxel: Meaningful improvement in metastasis-free survival: Metastasis-free survival improved to 15.34 months (DP) versus 7.7 months (D, HR=0.52, p=0.0012), consistent with Plinabulin’s DC maturation and durable anti-cancer benefit...The incidence of new brain metastasis was reduced to 4.32% (DP) vs. 7.83% (D), consistent with Plinabulin’s brain-penetrant properties which demonstrated survival benefit in glioblastoma anal model as a monotherapy."

P3 data • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

BeyondSpring plans to initiate a global Phase 3 DUBLIN-4 trial following its End-of-Phase 2 meeting with the U.S. FDA. (GlobeNewswire) - "This study will evaluate Plinabulin + docetaxel vs. docetaxel in non-squamous EGFR wild-type NSCLC after progression on anti-PD-(L)1 and chemotherapy, and is intended to serve as the global confirmatory study."

New P3 trial • Lung Non-Squamous Non-Small Cell Cancer

Plinabulin and Selumetinib Enhance M1 Macrophage Traits and Trigger Cell Death in AML (ASH 2024) - "Additionally, both drugs were associated with reduced mitochondrial membrane potential in leukemic blasts and AAMs, suggesting an impact on mitochondrial metabolism. In conclusion, we found that both BPI-2358 and AZD6244 exhibit potential in repolarizing M2-like TAMs towards an M1-like phenotype, and have cytotoxic activity in AAM and leukemic blasts thus representing a promising avenue for enhancing AML treatment strategies."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • CD163 • CD34 • CD80 • CD86 • HOXA9 • KIT • MN1 • MRC1 • TNFA

Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Lyudmila Bazhenova, M.D. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Resensitize Patients with Eight Cancer Types Who Failed Prior PD-1/L1 Inhibitors with Disease Control Rate of 54% through DC Maturation and M1 Macrophage Polarization via GEF-H1-dependent Mechanism in Phase 1 Clinical Study (GlobeNewswire) - "This phase 1 investigator-initiated study (NCT04902040, MD Anderdon Cancer Center) shows that in addition to potent DC maturation for a systemic immune response, plinabulin combined with radiation and PD-1 inhibitor promotes proinflammatory monocytes and M1 macrophage polarization via a Plinabulin specific GEF-H1-dependent mechanism with the potential of overcoming acquired resistance to immune checkpoint inhibitors from pro-tumor macrophages."

P1 data • Hepatocellular Cancer • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Resensitize NSCLC Patients Who Progressed on Prior PD-1/L1 Inhibitors with Disease Control Rate of 85% in Phase 2 Clinical Study (GlobeNewswire) - "New data from a phase 2 investigator-initiated study (NCT05599789, Peking Union Hospital China) evaluating Plinabulin, docetaxel, and pembrolizumab in metastatic NSCLC patients who progressed on prior PD-1/L1 inhibitors (n=47), showed encouraging efficacy and safety data. The combination demonstrated median progression-free survival (PFS) of 7.0 months, confirmed objective response rate (ORR) of 18.2%, duration of response (DOR) of 7.2 months, disease control rate (DCR) of 85%, and 12-month overall survival (OS) rate at 79%, and 24-month OS rate at 66% (median OS not reached)."

P2 data • Non Small Cell Lung Cancer

A Phase 2 triplet study of plinabulin/docetaxel/pembrolizumab for metastatic NSCLC immediately after progression on immune-checkpoint-inhibitor alone or in combination: efficacy and biomarker analysis (SITC 2025) - P2 | "Whole blood analysis indicated higher proportions of activated CD4+/CD8+ T-cells post treatment.Trial Registration NCT05599789Ethics Approval The study was approved by the Ethics Committee of Peking Union Medical College Hospital (Ethics Approval Number: I-22PJ575).Consent No sensitive or identifiable information was contained in the abstract.Abstract 1330 Table 1View inline•Open as popup303 Study Phase 2 efficacy summary. A Phase 2 triplet study of plinabulin/docetaxel/pembrolizumab for metastatic NSCLC immediately after progression on immune-checkpoint-inhibitor alone or in combination: efficacy and biomarker analysis"

Biomarker • Checkpoint inhibition • Clinical • IO biomarker • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • APC • CD4 • CD8

Immune Activation with Plinabulin Promotes Monocyte-Macrophage Responses Combining Radiation with Immune Checkpoint Blockade (ICB) in ICB-Relapsed/Refractory Tumors (SITC 2025) - P1/2 | "There was no baseline difference in TIIC-associated GEF-H1 immune scores between PR+SD and PD groups, whereas total MoMac-associated GEF-H1 immune score was higher in PD group when compared to PR+SD group. Further subgroup analysis of MoMac I-IV suggests that AGR1+ MoMac-III may represent the dominating pro-tumor M2 phenotype and that plinabulin combined with RT+ICB drives differential monocyte-macrophage responses in responders.Conclusions In addition to maturation of DCs to generate a systemic immune response, plinabulin combined with radiation and ICB promotes proinflammatory monocytes and M1 polarization via a GEF-H1-dependent mechanism with the potential of overcoming acquired ICB resistance from pro-tumor macrophages.Ethics Approval Among the 19 patients evaluable for safety, 1 male (Hispanic or Latino) patient entered 'other' ethnics and should be added to the 18 patients under 'Racial Categories'."

Checkpoint block • Checkpoint inhibition • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD14

Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Lyudmila Bazhenova, M.D. | Trial completion date: Jun 2025 ➔ Oct 2025 | Trial primary completion date: Jul 2022 ➔ Nov 2024

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Dynamic Microtubules as Sensors in Animal Cells. (PubMed, Biophys J) - "The microtubule destabilizing drugs colchicine and plinabulin may mimic sensing of pathophysiological cues by microtubules, leading to activation gene expression programs that promote cell survival, growth and repair which account for the therapeutic actions of the drugs. In tissue cells with stable morphologies, the sensory functions of microtubules may be as or more important than their architectural functions. This re-framing of microtubule biology suggests new directions for mechanistic inquiry and drug discovery."

Journal • Review

Clinical and Translational Responses to Plinabulin, Radiation, and Anti-PD-1 in Relapsed Refractory Classical Hodgkin Lymphoma (SOHO 2025) - P1/2 | " Patients received plinabulin (30 mg/m2) C1D1 and 4 and C2D1 q4 week cycle, nivolumab (240 mg D1, 15), and focal radiation to 20 Gy in 5 fractions starting C1D1. There are limited treatment options for patients with RRHL after ICB, BV, and stem cell transplant. Heavily pretreated patients with RRHL responded well to plinabulin, ICB, and radiation. Translational analysis in these patients supports treatment-specific enhanced immune activation with treatment."

Clinical • IO biomarker • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • CD4 • CD8 • CDK1

The Novel Diketopiperazine Derivative, Compound 5-3, Selectively Inhibited the Proliferation of FLT3-ITD Mutant Acute Myeloid Leukemia (AML) Cells. (PubMed, Mar Drugs) - "Plinabulin is a diketopiperazines derivative that exhibits extensive anti-cancer potency by targeting β-tubulin...In conclusion, the study identified diketopiperazine derivative as a novel FLT3-ITD selective inhibitor. These results demonstrated that 5-3 might be a drug candidate for the treatment of FLT3-ITD-positive AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • STAT5

BeyondSpring Publishes Human Clinical Study in Med (Cell Press) Showing Plinabulin-Driven Dendritic Cell Maturation and Tumor Response After Prior Checkpoint Inhibitor Failure (The Manila Times) - P1b/2 | N=19 | NCT04902040 | "Nineteen patients received the combination regimen-14 on pembrolizumab and 5 on nivolumab. Tumor responses were evaluable in 13 ICI-relapsed patients across eight tumor types. Objective response rate (ORR) was 23%, and disease control rate (DCR) was 54%. Clinically meaningful benefits (PR, partial response; SD, stable disease) were observed in NSCLC (2/2), HNSCC (2/3), and Hodgkin lymphoma (2/2). Both Hodgkin lymphoma patients had durable responses exceeding 19 months despite 12-16 prior lines of therapy. Mechanism Confirmation: Plinabulin triggered DC maturation post-RT via GEF-H1 signaling. Flow cytometry of whole blood revealed increased expression of DC maturation markers (CCR7, CD80, CD83) and a shift in monocyte subpopulations from classical to proinflammatory phenotype in responders."

P1/2 data • Hodgkin Lymphoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers. (PubMed, Med) - P1/2 | "These preliminary results provide a rationale for testing RT/plinabulin/ICI combination in future post-ICI-failure confirmatory trials."

Checkpoint inhibition • Journal • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PLINABULIN AND SELUMETINIB INDUCE AAMS REPROGRAMMING INTO M1-LIKE MACROPHAGES AND REDUCE AML CELL VIABILITY (EHA 2025) - "We then evaluated gene expression changes under the combination treatment of AZD6244 and revumenib (a Menin inhibitor) to assess AAM repolarization. In conclusion, we found that BPI-2358 and AZD6244 can reprogram AAMs into M1-like macrophages, enhancing their pro-inflammatory features and phagocytic capacity while reducing AAM-CD163⁺ levels and AML viability, representing a promising therapeutic approach in combination with targeted therapies in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD163 • CD34 • CD80 • KIT • MN1 • MRC1 • NOS2 • TNFA

Phase 2 study of pembrolizumab (pembro) plus plinabulin (plin) and docetaxel (doc) for patients (pts) with metastatic NSCLC after progression on first-line immune checkpoint inhibitor alone or combination therapy: Initial efficacy and safety results on immune re-sensitization. (ASCO 2025) - P2 | "Pembro plus plin and doc in pts with metastatic NSCLC who developed PD on ICI shows promising efficacy, with doubling PFS and DCR compared with historical data of doc. The AEs of the triple combination treatment is manageable. Further investigations into which pts would benefit from continued ICI treatment after progression is warranted."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Cardiovascular • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • APC • EGFR

BeyondSpring Announces Poster Presentation at 2025 ASCO Annual Meeting (The Manila Times) - "BeyondSpring Inc...today announces that it will have a poster presentation on 303 Study, the investigator-initiated study supported by Merck...and BeyondSpring in 2L/3L NSCLC who progressed on PD-1/PD-L1 inhibitors at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place on May 30 through June 3 in Chicago, IL."

P2 data • Non Small Cell Lung Cancer

BeyondSpring Reports 2024 Year-End Financial Results and Highlights Key Clinical & Strategic Milestones (GlobeNewswire) - "Expected 2025 Milestones - Plinabulin: 1H 2025: Updated data from Phase 2 of Study 303 in metastatic NSCLC progressed on PD-1/PD-L1 inhibitors. 2H 2025: Preliminary data from Phase 2 of Study 302 in 1L ES-SCLC. SEED: Mid-2025: Expected IND filing of RBM39 degrader. 2H 2025: RBM39 degrader expected to begin patient enrollment. 2H 2025: Tau degrader expected to achieve in vivo efficacy."

IND • New trial • P2 data • Non Small Cell Lung Cancer • Small Cell Lung Cancer